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通过内镜超声活检测序来描述胃肠道间质瘤并评估新辅助伊马替尼治疗。

Characterizing gastrointestinal stromal tumors and evaluating neoadjuvant imatinib by sequencing of endoscopic ultrasound-biopsies.

机构信息

Division of Medical Gastroenterology, Department of Internal Medicine, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden.

Department of Surgery, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden.

出版信息

World J Gastroenterol. 2017 Aug 28;23(32):5925-5935. doi: 10.3748/wjg.v23.i32.5925.

DOI:10.3748/wjg.v23.i32.5925
PMID:28932084
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5583577/
Abstract

AIM

To evaluate endoscopic ultrasound (EUS)-guided biopsies for the pretreatment characterization of gastrointestinal stromal tumors (GIST) to personalize the management of patients.

METHODS

All patients with lesions suspected to be GIST who were referred for EUS-sampling at a tertiary Swedish center were eligible for inclusion 2006-2015. During the observational study phase (2006-2011), routine fine-needle-aspiration (EUS-FNA) was performed. In 2012-2015, we converted to an interventional, randomized protocol with dual sampling EUS-FNA and fine-needle-biopsy-sampling (EUS-FNB) for all lesions. c-KIT- and DOG-1-immunostaining was attempted in all samples and a manual count of the Ki-67-index was performed. FNB-sampled tissue and the resected specimens were subjected to Sanger sequencing of the and platelet-derived growth factor alpha () genes.

RESULTS

In all, 64 unique patients with GIST were included, and of these, 38 were subjected to pretreatment dual sampling. EUS-FNB had a higher diagnostic sensitivity when compared head-to-head with EUS-FNA (98% 58%, < 0.001) and was more adequate for Ki-67-indexing (Ki-67) (92% 40%, < 0.001). Sequencing of EUS-biopsies was successful in 43/44 (98%) patients, and the mutation profiles (-mutation 73%, -mutation 18%, wild-type 7%) were fully congruent with those detected in the corresponding resected specimens. In imatinib-naïve patients, the Ki-67 was comparable with the Ki-67-index in the corresponding surgical specimens (Ki-67) (2.7% 2.9%, = 0.68). In patients treated with neoadjuvant imatinib who also carried mutations indicating sensitivity, the Ki-67 was higher than the Ki-67 (2.5% 0.2%, = 0.005), with a significant reduction in the Ki-67-index of -91.5% (95%CI: -82.4 to -96.0, = 0.005).

CONCLUSION

EUS-guided biopsy sampling is accurate for the pretreatment diagnosis and characterization of GISTs and allows the prediction and evaluation of tumor response to neoadjuvant imatinib therapy.

摘要

目的

评估内镜超声(EUS)引导下活检术在胃肠道间质瘤(GIST)的术前评估中的作用,以实现个体化治疗。

方法

2006 年至 2015 年,在瑞典的一家三级中心,所有疑似 GIST 病变并接受 EUS 取样的患者均符合纳入标准。在观察性研究阶段(2006-2011 年),进行常规细针抽吸(EUS-FNA)。2012-2015 年,我们采用介入性、随机方案,对所有病变进行 EUS-FNA 和细针活检(EUS-FNB)双重取样。所有样本均尝试进行 c-KIT 和 DOG-1 免疫染色,并进行 Ki-67 指数的手动计数。FNB 取样组织和切除标本均进行 和血小板衍生生长因子 α()基因的 Sanger 测序。

结果

共纳入 64 例 GIST 患者,其中 38 例患者行术前双重取样。与 EUS-FNA 相比,EUS-FNB 的诊断敏感性更高(98% 比 58%,<0.001),并且更适合 Ki-67 指数(Ki-67)检测(92% 比 40%,<0.001)。44 例(98%)EUS 活检成功进行测序,突变谱(-突变 73%,-突变 18%,野生型 7%)与相应切除标本的检测结果完全一致。在未接受伊马替尼治疗的患者中,Ki-67 与相应手术标本的 Ki-67 指数(Ki-67)相似(2.7% 比 2.9%,=0.68)。在接受新辅助伊马替尼治疗且携带敏感性突变的患者中,Ki-67 高于 Ki-67(2.5% 比 0.2%,=0.005),Ki-67 指数降低 91.5%(95%CI:-82.4 至-96.0,=0.005)。

结论

EUS 引导下的活检取样术对 GIST 的术前诊断和特征评估准确,并可预测和评估新辅助伊马替尼治疗的肿瘤反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b5/5583577/df8542782fac/WJG-23-5925-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b5/5583577/2275eadbcfe6/WJG-23-5925-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b5/5583577/9e1ff9ced302/WJG-23-5925-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b5/5583577/ac486ba52dac/WJG-23-5925-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b5/5583577/df8542782fac/WJG-23-5925-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b5/5583577/2275eadbcfe6/WJG-23-5925-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b5/5583577/9e1ff9ced302/WJG-23-5925-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b5/5583577/ac486ba52dac/WJG-23-5925-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b5/5583577/df8542782fac/WJG-23-5925-g004.jpg

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